1. Field of the Invention
The present invention relates to a method of preparing a solid form of racemic or optically active D or L-α-glycerophosphorylcholine, and more particularly, to a method of preparing a solid form of racemic or optically active D or L-α-glycerophosphorylcholine from a conventional liquid phase of racemic or optically active D or L-α-glycerophosphorylcholine through phase change using an organic solvent.
2. Description of Related Art
Racemic or optically active D or L-α-glycerophosphorylcholine is a compound represented by Formula 1 below, and is known to have excellent effects in treatment of senile cognitive impairment (decreased memory, confusion, loss of sense of direction, decreased motivation and spontaneity, decreased concentration) such as secondary symptoms due to cerebrovascular deficiency and degenerative organic brain syndromes and senile pseudo-depression such as emotional and behavioral changes (anxiety disorder, irritability, lack of interest), and specifically, is known to be an excellent drug that normalizes functions of damaged neurons and abnormalities of the cholinergic system due to acetylcholine deficiency by promoting production of acetylcholine, a neurotransmitter in the brain.
                wherein * indicates a chiral center and Formula 1 represents a racemic and optically active D or L-α-optical isomer.        
Known methods of crystallizing liquid-phase α-glycerophosphorylcholine are as follows. First of all, in J. Am. Chem. Soc. 70, 1394-1399 (1948), it was reported that a water-containing glycerophosphorylcholine prepared by a pure synthetic method can be solidified in an alcohol solution, but no specific crystallization method or crystal structure was mentioned.
According to a method disclosed in Korean Patent No. 262,281, glycerophosphorylcholine is prepared by performing deacylation reaction by alcoholysis in a reactor containing basic ion exchange resins, lipophilic impurities are removed using non-polar adsorptive resins, the glycerophosphorylcholine is dissolved in methanol, to which an about 20-fold amount of n-butanol is further added, and then the mixture is subjected to vacuum concentration, followed by cooling and filtering to recover anhydrous crystals. However, in this method, it was reported that microcrystals having high hygroscopicity were formed, and there was no mention of specific crystal structure.
According to methods disclosed in Korean Patent Application Publications No. 10-2013-0063520 and No. 10-2013-0063521, conventional liquid-phase L-α-glycerophosphorylcholine is concentrated, dissolved in an alcohol solution, and seed crystals are added to trigger crystallization, followed by aging and filtering to obtain crystals of L-α-glycerophosphorylcholine in anhydrous form and L-α-glycerophosphorylcholine-type in the form of a monohydrate. However, the above methods have problems in that the methods use seed crystals and that yield is low due to crystal formation by difference in solubility.
According to a method disclosed in Korean Patent Application Publication No. 10-2001-7005577, L-carnitine, which is a hygroscopic solid, is polished with acetone and filtered to obtain solid L-carnitine. Until now, there has been no method of preparing solid glycerophosphorylcholine by such a method.
Accordingly, the present inventors have made intensive efforts to solve the problems of the conventional technologies, and as a result, have developed a method to solidify racemic or optically active D or L-α-glycerophosphorylcholine in a simpler and easier way and confirmed that the solidified D or L-α-glycerophosphorylcholine may be mass-produced at high purity and low cost, and thus the present invention was completed.